MassIVE MSV000084855

Imported Reanalysis Dataset Public PXD009012

ARIH2 is a novel Vif-dependent regulator of CUL5-mediated APOBEC3G degradation in HIV infection

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Description

Discovery of novel host-virus interactions leads to a better understanding of mechanisms underlying infection and points to potential therapeutic targets at the interface between virus and host proteins. Recently, global, virus-host interaction networks have been mapped using affinity purification-mass spectrometry (AP-MS) approaches, but these studies do not provide information about dynamic remodeling of host complexes during infection. Here, we describe a novel quantitative proteomics approach in the context of HIV infection to unravel dynamics of the Cullin RING E3 ligase 5 (CRL5) complex, which is hijacked by HIV Vif to degrade the viral restriction factor of the APOBEC3 family. Generating a dynamic and quantitative interaction network of CRL5 under various infection conditions, we identify the E3 ligase ARIH2 as novel regulator of APOBEC3G degradation, which is essential for HIV infectivity in primary CD4+ T-cells. ARIH2 acts in a “tag-team” mechanism that accelerates ubiquitin chain formation on APOBEC3G through CUL5Vif/CBFß by priming the substrate with mono-ubiquitination. Finally, our data suggest a general role for ARIH2 in CRL5 substrate ubiquitination in host cells. [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: host-virus interactions ; AP-MS ; ARIH2 ; CUL5 ; Cullin RING E3 ligases ; HIV ; MassIVE.quant reviewed - Gold

Contact

Principal Investigators:
(in alphabetical order) 		Nevan J. Krogan, University of California San Francisco, N/A
Submitting User: ccms

Publications

Hüttenhain R, Xu J, Burton LA, Gordon DE, Hultquist JF, Johnson JR, Satkamp L, Hiatt J, Rhee DY, Baek K, Crosby DC, Frankel AD, Marson A, Harper JW, Alpi AF, Schulman BA, Gross JD, Krogan NJ.
ARIH2 Is a Vif-Dependent Regulator of CUL5-Mediated APOBEC3G Degradation in HIV Infection.
Cell Host Microbe. 2019 Jul 10;26(1):86-99.e7. Epub 2019 Jun 25.

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Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

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